Banche Niclot Alessia Giovanna Santa, Marini Elena, Ferrero Ivana, Barbero Francesco, Rosso Elena, Fenoglio Ivana, Barge Alessandro, Pessina Augusto, Coccè Valentina, Paino Francesca, Mareschi Katia, Fagioli Franca
Department of Public Health and Paediatrics, The University of Turin, Piazza Polonia 94, 10126 Torino, Italy.
Stem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children's Hospital, City of Health and Science of Turin, 10126 Torino, Italy.
Pharmaceutics. 2023 Sep 19;15(9):2340. doi: 10.3390/pharmaceutics15092340.
Osteosarcoma (OS) represents a rare cancer with an unfavorable prognosis that needs innovative treatment. The aim was to isolate a secretome from mesenchymal stem cells (MSCs) that are treated with paclitaxel (PTX)-containing microvesicles as a drug delivery system and analyze its cytotoxic effects on OS cell lines (SJSA, MG63, and HOS).
Three batches of secretome (SECR-1, SECR-2, and SECR-3) were produced from three bone marrow (BM) MSCs samples treated for 24 h with 15 µg/mL of PTX or with a standard medium. The viability of the OS cell lines after 5 days of exposure to SECR-1-2-3 (pure and diluted to 1:2 and 1:4) was analyzed with an MTT assay. The same SECR batches were analyzed with high-performance liquid chromatography (HPLC) and with a nanoparticle tracking assay (NTA).
A statistically significant decrease in the viability of all OS cell lines was observed after treatment with SECR-PTX 1-2-3 in a dose-response manner. The NTA analyses showed the presence of nanoparticles (NPs) with a mean size comparable to that of extracellular vesicles (EVs). The HPLC analyses detected the presence of PTX in minimal doses in all SECR batches.
This proof-of-concept study showed that the conditioned medium isolated from MSCs loaded with PTX had a strong cytotoxic effect on OS cell lines, due to the presence of EV and PTX.
骨肉瘤（OS）是一种罕见的癌症，预后不佳，需要创新的治疗方法。目的是从经含紫杉醇（PTX）微泡处理作为药物递送系统的间充质干细胞（MSC）中分离分泌组，并分析其对骨肉瘤细胞系（SJSA、MG63和HOS）的细胞毒性作用。
从三个骨髓（BM）MSC样本中制备三批分泌组（SECR-1、SECR-2和SECR-3），这些样本分别用15μg/mL的PTX或标准培养基处理24小时。用MTT法分析OS细胞系在暴露于SECR-1-2-3（纯品以及稀释至1:2和1:4）5天后的活力。用高效液相色谱（HPLC）和纳米颗粒跟踪分析（NTA）对相同的SECR批次进行分析。
用SECR-PTX 1-2-3处理后，所有OS细胞系的活力均以剂量反应方式出现统计学上的显著下降。NTA分析显示存在平均大小与细胞外囊泡（EV）相当的纳米颗粒（NP）。HPLC分析在所有SECR批次中均检测到极少量PTX的存在。
这项概念验证研究表明，由于存在EV和PTX，从负载PTX的MSC中分离出的条件培养基对OS细胞系具有强烈的细胞毒性作用。
